February // 2021 // njretina.com

Physicians Retinal Artery Occlusions Nneka O. Brooks, MD Retinal artery occlusions are a rare but serious ocular finding. In addition to causing permanent Nicholas D. Chinskey, MD vision loss or deficits, retinal artery occlusions may portend a serious underlying medical issue Rishabh Date, MD and are associated with a significant risk for subsequent and cardiovascular disease. As such, Leonard Feiner, MD, PhD retinal artery occlusions provide an opportunity for timely diagnosis by an eyecare specialist to be Howard F. Fine, MD, MHSc truly life-saving. Eric S. Friedman, MD Luis A. Gonzalez, MD, MPH In this review, we present three cases that highlight the variable causes of retinal artery Paul Hahn, MD, PhD occlusions and the need for prompt systemic workup in patients with this diagnosis. Vincent Y. Ho, MD Bruce J. Keyser, MD Case 1: David Y. Kim, MD A 44-year-old man with no known past medical history presented with one week of vision changes in the left . He reported the sudden onset of a “shade” blocking the bottom half of Jennifer M. Krawitz, MD his vision in the left eye. There was no associated eye pain, flashes, floaters or headache, so he Marisa K. Lau, MD did not present for evaluation initially because he thought his symptoms would resolve. On Steven A. Madreperla, MD, PhD examination, his vision was 20/20 in the right eye and 20/25 in the left. Intraocular pressure Lekha K. Mukkamala, MD was normal in each eye. There was a subtle afferent pupillary defect in the left eye and a dense Megan M. Nichols, MD scotoma of the inferior visual field was noted on confrontational testing in the left eye. Stuart W. Noorily, MD Akosua Nti, MD examination was normal in the right eye, but in the left eye demonstrated diffuse Alexander D. Port, MD whitening of the superior hemi- as well as an intravascular thrombus consistent with Jonathan L. Prenner, MD a retinal artery occlusion (Figure 1). Daniel B. Roth, MD Christopher M. Seery, MD Sumit P. Shah, MD Harris Sultan, MD, MS Elizabeth Tegins, MD Vinod B. Voleti, MD H. Matthew Wheatley, MD

Locations North Jersey Central Jersey Belleville Bridgewater 973-450-5100 908-218-4303 Elizabeth Eatontown 908-409-4900 732-389-2333 Morristown Edison 973-630-7700 732-906-1887 Ridgewood Lakewood 201-445-6622 732-363-2396 Teaneck Lawrenceville 201-837-7300 609-896-3655 Union City Monroe 201-867-2999 609-655-8301 Vauxhall New 908-349-8155 Brunswick Figure 1 Wayne 732-220-1600 973-633-9898 Toms River 732-797-3883 The patient was sent directly to the Emergency Department for prompt evaluation and workup. A transthoracic echocardiogram was performed which revealed severe aortic valve calcification and aortic stenosis due to a congenital bicuspid valve. The patient was started on systemic anticoagulation by cardiology and underwent an aortic valve replacement shortly thereafter. The AVR surgery was done to mitigate risk of subsequent ischemic events and thus the retinal diagnosis led identifying and fixing a more serious problem.

Case 2: An 80-year-old woman with a history of systemic hypertension presented for evaluation of a sudden-onset painless “shade” coming down over the top half of her vision in the right eye. Visual acuity was 20/20 in each eye but there was a superonasal visual field defect on confrontational testing in the right eye. Fundus examination demonstrated a Hollenhorst plaque near the inferior margin and retinal whitening along the inferotemporal arcade. Fluorescein was obtained which demonstrated markedly delayed and partially obstructed flow within the inferotemporal arteriole, consistent with branch retinal artery occlusion (Figure 2). Of note, fundus autofluorescence images highlighted calcific plaques at the disc margin in both , including the asymptomatic left eye (Figure 3A and 3B).

Figure 2

Figure 3A and 3B

The patient was sent to the hospital for prompt evaluation. EKG OCT scan of the left eye showed significant thickening and was remarkable for atrial fibrillation and hyperlipidemia was intracellular edema of the inner retinal layers, but relative noted on laboratory testing. The patient was started on systemic preservation of the outer retina, consistent with a central retinal anticoagulation and a statin and was discharged from the hospital artery occlusion disrupting blood flow to the inner retina. with a Holter monitor and further follow-up with cardiology. The patient’s was checked in the office and found to be 210/138 mmHg. He was sent directly to the emergency Case 3: department for management of hypertensive urgency. His blood A 61-year-old man with no known past medical history presented pressure improved with medications and he was admitted to the with five days of vision loss in the left eye. He described the sudden, hospital for titration of blood pressure medications and workup. painless onset of a black area in the left eye that had gotten larger and denser since onset. He could no longer make out shapes or figures in the left eye.

On examination, visual acuity was 20/20 in the right eye and hand motions in the left eye. There was an afferent pupillary defect in the left eye. Anterior examination was otherwise normal for age. Dilated Figure 4 fundus exam in the right eye demonstrated arteriolar attenuation and A-V nicking. In the left eye, there was marked retinal whitening along the arcades and in the macula as well as a “cherry-red spot” consistent with a central retinal artery occlusion (Figure 4).

 Februray // 2021 // njretina.com // 2 Discussion: Finally, can be used to assess ocular Retinal artery occlusion (RAO) including central retinal artery perfusion and will demonstrate significantly delayed arterial filling occlusion and branch retinal artery occlusion are serious and times in RAO (Figure 3). Unfortunately, there are no evidence- urgent diagnoses. Prompt referral and expedited workup can based ocular therapies for retinal artery occlusion, so the main be truly life-saving in many cases of retinal artery occlusion and emphasis of care is to identify systemic risk factors or embolic may reveal serious conditions such as carotid atherosclerosis, sources and enable appropriate systemic therapy.1,3,4 Eye care atrial fibrillation, cardiac valve disease and others.1 providers may measure the patient’s blood pressure, administer a chewable aspirin and consider IOP-lowering therapies for acute Correctly diagnosing RAO may be difficult depending on the presentations. Heroics such as intravenous tPA (“clot-busters”) patient’s presentation. Retinal whitening takes several hours to or YAG to the thrombus are not recommended owing to the become pronounced and may resolve after several days or high risk of complications and lack of proven benefit.1 In the eye weeks. Retinal whitening may not be present in patients care setting, the main focus remains correct diagnosis and timely presenting immediately after symptom onset or in cases of referral to enable secondary prevention of further embolic events.1,3,4 delayed presentation. Emboli are often difficult to appreciate ophthalmoscopically and may break up with time. In a patient Acute, symptomatic retinal artery occlusion is considered a stroke with concerning symptoms of sudden painless vision loss, equivalent.1,5 Patients presenting within a week of RAO symptom in-office imaging is helpful to establish the correct diagnosis of onset are at extremely elevated risk of stroke and cardiovascular RAO. Fundus photography provides static, editable images and complications and should be sent to the nearest stroke center or may help identify emboli that are difficult to appreciate capable ED for urgent evaluation.6,5 At minimum, workup should funduscopically (Figure 1). include an electrocardiogram to rule out cardiac arrhythmia, echocardiogram to look for cardiac valve calcification or structural Fundus auto-fluorescence is especially helpful for identifying heart disease, carotid imaging to evaluate for atherosclerosis small emboli because calcium- containing emboli are brightly and a CT or MRI brain to rule-out concurrent stroke (Table 1). In hyper auto-fluorescent and are readily apparent on FAF images patients younger than 50, laboratory testing should include causes (Figure 3 A/B). of hypercoagulability and vasculitis such as antiphospholipid antibodies, Factor V Leiden and malignancy. In patients older OCT imaging is also very helpful in the identification of acute and than 50 years of age, it is prudent to include giant cell arteritis chronic RAO. In acute artery occlusion, OCT demonstrates marked in the differential and to include ESR, CRP and platelets in lab inner retinal edema with loss of the cell layer distinctions. Owing testing and consider starting steroids and arranging for temporal to the dual retinal circulation, the inner retina is supplied by the artery biopsy if there is any clinical suspicion of GCA. retinal vessels, and thus becomes ischemic in RAO, whereas the outer retinal layers are supplied by the choroid and remain relatively Although vision is unlikely to improve after RAO, it is nonetheless preserved in RAO.2 Weeks to months after RAO, the edema resolves, necessary to monitor these patients closely to ensure that no and the ischemic inner retina atrophies, resulting in marked retinal retinal or iris neovascularization develop. If neovascularization does thinning and loss of the inner retinal layers, again with relative develop, this complication can be treated with Anti-VEGF injections preservation of the outer retinal layers – this finding is often most followed by panretinal photocoagulation to the ischemic retina. readily apparent on the macular thickness scan which reveals Patients with poor vision in one eye after RAO should be advised diffuse thinning in CRAO or sectoral thinning that respects the to follow monocular precautions to help prevent vision loss in horizontal and is confined to a vascular territory in the case the fellow eye. of BRAO.

References: 1. Olsen TW, Pulido JS, Folk JC, et al. Retinal and Ophthalmic Artery Occlusions Preferred Practice Pattern®. 2017;124:P120–P143. 2. Ryan SJ, Schachat AP, Wilkinson CP, et al. Retina. London: Elsevier Health Sciences; 2018. 3. Dattilo M, Biousse V, Newman NJ. Update on the Management of Central Retinal Artery Occlusion. Neurol Clin 2017;35:83–100. 4. Biousse V, Nahab F, Newman NJ. Management of Acute Retinal Ischemia: Follow the Guidelines! Ophthalmology 2018;125:1597–1607. 5. Lavin P, Patrylo M, Hollar M, et al. Stroke Risk and Risk Factors in Patients With Central Retinal Artery Occlusion. Am J Ophthalmol 2018;196:96–100. 6. Park SJ, Choi N-K, Yang BR, et al. Risk and Risk Periods for Stroke and Acute Myocardial Infarction in Patients with Central Retinal Artery Occlusion. Ophthalmology 2015;122:2336- 2343.e2.

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 Februray // 2021 // njretina.com // 3 At the Forefront of Clinical Research At the Forefront of Clinical Research NJRetina currently conducts clinical trials at key locations. Our clinical research coordinators who conduct the trials will be happy to discuss the inclusion/ exclusion criteria or any other aspect of these studies with you or your patients. If you have any questions, please feel free to contact:

Véronique Ruppe, PhD, Clinical Trials Manager - PRISM Vision Group: 908-258-8323 Joe Martinez - Teaneck: 201-837-7300; 4 Dina Christodoro - Toms River: 732-797-3984 Amy Leviton - Edison: 732-906-1887

Enrolling Studies: Dry AMD Teaneck & Edison (Closed) A Genetic and Registry Study to Evaluate Long-term Clinical Outcomes and Disease Progression in Subjects with Non-Central Geographic Soon to Enroll Studies: Atrophy (GA) Who Are Carriers of High-Risk Genetic Complement Variants Associated with Dry Age-related (AMD) A Dry AMD: Prospective Natural History Study to Evaluate Clinical Characteristics and • A Phase 2 Multicenter, Randomized, Double-Masked, Sham-Controlled Disease Progression in Subjects with Non-Central Geographic Atrophy (GA) Study of the Safety and Efficacy of Intravitreal Injections of NGM621 in Subjects with Geographic Atrophy (GA) Secondary to Age-Related Who Are Carriers of High-Risk Genetic Variants of Complement Factor H Macular Degeneration (AMD) (NGM study) – Teaneck (CFH) Wet AMD: Teaneck (Closed) • A Randomized, Double-Masked, Active-Controlled Phase 2/3 Study Phase II, Randomized, Double-Masked, Placebo-Controlled Clinical Study of the Efficacy and Safety of High - Dose Aflibercept in Patients with to Evaluate the Safety, Efficacy, and Pharmacokinetics of Subcutaneous Neovascular Age-Related Macular Degeneration (Pulsar) – Teaneck Injections of Elamipretide in Subjects with Age-Related Macular and Edison Degeneration with Geographic Atrophy (SPIAM) : • A Phase 2, Randomized, Dose-escalation, Observation-controlled Teaneck & Toms River Study to Evaluate the Efficacy, Safety, and Tolerability of RGX-314 A Phase II, Multi-Center, Randomized, Single-Masked, Sham Injection Gene Therapy Delivered via One or Two Suprachoroidal Space (SCS) Controlled Study of the Safety, Tolerability, and Evidence of Activity of Injections in Participants with Diabetic Retinopathy (DR) Without Center Intravitreal Injection of R7171009 in Patients with Geographic Involved-Diabetic Macular Edema (CI-DME) (ALTITUDE) – Teaneck Atrophy Secondary to Age-Related Macular Degeneration (Gallego)

Vauxhall A Study of Disease Progression in Genetically Defined Patients with Geographic Atrophy Secondary to Age-Related Macular Degeneration (Gyroscope)

Wet AMD Edison and Teaneck (Closed) A Randomized, Single-Masked, Active-Controlled Phase 2 Study of the Safety, Tolerability, and Efficacy of Repeated Doses of Hight-Dose Aflibercept in Patients with Neovascular Age-Related Macular Degeneration

 Februray // 2021 // njretina.com // 4